Evidence for ubiquitin-regulated nuclear and subnuclear trafficking among Paramyxovirinae matrix proteins

PLoS Pathogens
Mickey PentecostBenhur Lee

Abstract

The paramyxovirus matrix (M) protein is a molecular scaffold required for viral morphogenesis and budding at the plasma membrane. Transient nuclear residence of some M proteins hints at non-structural roles. However, little is known regarding the mechanisms that regulate the nuclear sojourn. Previously, we found that the nuclear-cytoplasmic trafficking of Nipah virus M (NiV-M) is a prerequisite for budding, and is regulated by a bipartite nuclear localization signal (NLSbp), a leucine-rich nuclear export signal (NES), and monoubiquitination of the K258 residue within the NLSbp itself (NLSbp-lysine). To define whether the sequence determinants of nuclear trafficking identified in NiV-M are common among other Paramyxovirinae M proteins, we generated the homologous NES and NLSbp-lysine mutations in M proteins from the five major Paramyxovirinae genera. Using quantitative 3D confocal microscopy, we determined that the NES and NLSbp-lysine are required for the efficient nuclear export of the M proteins of Nipah virus, Hendra virus, Sendai virus, and Mumps virus. Pharmacological depletion of free ubiquitin or mutation of the conserved NLSbp-lysine to an arginine, which inhibits M ubiquitination, also results in nuclear and nucleolar ...Continue Reading

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Citations

Jun 5, 2015·Cellular Microbiology·Stephen M Rawlinson, Gregory W Moseley
Sep 9, 2016·Molecular Therapy. Methods & Clinical Development·Arnold ParkBenhur Lee
Aug 24, 2016·PloS One·Xuelian YuReena Ghildyal
Aug 23, 2017·Vaccines·Sarah van TolRicardo Rajsbaum
Sep 15, 2017·Journal of Virology·Luis Martinez-GilIsmael Mingarro
Apr 14, 2017·MSphere·Shannon M BeatyBenhur Lee
Aug 19, 2018·The Journal of Biological Chemistry·Friederike HansPhilipp J Kahle
Aug 9, 2016·The Journal of General Virology·Michelle D AudsleyGregory W Moseley
Oct 31, 2019·The Journal of Infectious Diseases·Marc RingelAndrea Maisner
Jun 29, 2016·FEBS Letters·Ruth E Watkinson, Benhur Lee
Aug 5, 2018·Nature Communications·Stephen M RawlinsonGregory W Moseley
Dec 4, 2019·The Journal of General Virology·Maria GüntherStefan Finke
Oct 7, 2020·Viral Immunology·Camilla M DonnellyJade K Forwood

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Methods Mentioned

BETA
ubiquitination
confocal microscopy
immunoprecipitation
co-IP
confocal microcopy
FACS
transfection
PCR
bimolecular fluorescence complementation
reverse phase chromatography

Software Mentioned

GeneMANIA
LI
QuikChange
Prism
Cytoscape
Clustal Omega
CRAPome
FlowJo
MudPIT
COR Odyssey

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